TY - JOUR
T1 - Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma
T2 - Analysis of Japanese patients in CheckMate 214 with extended follow-up
AU - Tomita, Yoshihiko
AU - Kondo, Tsunenori
AU - Kimura, Go
AU - Inoue, Takamitsu
AU - Wakumoto, Yoshiaki
AU - Yao, Masahiro
AU - Sugiyama, Takayuki
AU - Oya, Mototsugu
AU - Fujii, Yasuhisa
AU - Obara, Wataru
AU - Motzer, Robert J.
AU - Uemura, Hirotsugu
N1 - Funding Information:
This work was supported by Bristol-Myers Squibb and ONO Pharmaceutical Company Ltd. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant [P30 CA008748]. Authors received no financial support or compensation for publication of this manuscript.
Funding Information:
We thank the patients and their families for making this study possible. We also acknowledge the contributions of Sabeen Mekan, MD (formerly of Bristol-Myers Squibb) to the original data analyses and early development of the manuscript. Professional medical writing and editorial assistance were provided by Juan Sanchez-Cortes, PhD, and Lawrence Hargett of Parexel, funded by Bristol-Myers Squibb.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2019/12/23
Y1 - 2019/12/23
N2 - Background: Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods: CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-To-Treat (ITT) patients and safety (ITT patients). Results: Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months' minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19-1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62-2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3-4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions: Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.
AB - Background: Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods: CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-To-Treat (ITT) patients and safety (ITT patients). Results: Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months' minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19-1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62-2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3-4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions: Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.
KW - Japanese
KW - advanced renal cell carcinoma
KW - first-line treatment
KW - ipilimumab
KW - nivolumab
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U2 - 10.1093/jjco/hyz132
DO - 10.1093/jjco/hyz132
M3 - Article
C2 - 31633185
AN - SCOPUS:85076811868
SN - 0368-2811
VL - 50
SP - 12
EP - 19
JO - Japanese Journal of Clinical Oncology
JF - Japanese Journal of Clinical Oncology
IS - 1
ER -
